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CholangiocarcinomaPhase 2NCT04919642

Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma

A Phase 2 study testing TT-00420 in people with Cholangiocarcinoma and FGFR2 Fusion, run by TransThera Sciences (Nanjing), Inc. at 32 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is an open-label, multicenter study to evaluate the efficacy and safety of TT-00420 tablet in adult patients with advanced cholangiocarcinoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TT-00420
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
32 sitesUnited States
Study dates
7 Dec 2021to 28 Feb 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 18 years of age, at the time of signing informed consent
  • Histologically or cytologically documented advanced/metastatic or surgically unresectable cholangiocarcinoma who have received at least one line of prior systemic chemotherapy. Patients will be assigned to 1 of 4 cohorts:
  • Cohort A1: FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor
  • Cohort A2: FGFR2 fusions who have previously responded on at least one previous treatment with an FGFR inhibitor
  • Cohort B: other FGFR alterations, including FGFR2 mutations and FGFR1/3 alterations, including fusions
  • Cohort C: negative for FGFR alterations (FGFR wild-type)
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  • At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors5
  • Documentation of FGFR gene alteration status
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Hemoglobin (Hgb) ≥ 8 g/dl
  • Platelets (plt) ≥ 75 x 10^9/L
  • aspartate aminotransferase/serum glutamate oxaloacetate transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
  • Total bilirubin ≤ 1.5 x ULN
  • Calculated creatine clearance ≥ 50 mL/min (Cockcroft Gault formula
  • Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause
  • Must agree to take sufficient contraceptive methods to avoid pregnancy (including male and female participants) during the study and until at least 6 months after ceasing study treatment
  • Able to sign informed consent and comply with the protocol

Who cannot join

  • Women who are pregnant or lactating
  • Women of child-bearing potential (WOCBP) who do not use adequate birth control
  • Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g. evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases) Note: Patients with treated brain metastases that are off corticosteroids and have been clinically stable for 28 days are eligible for enrollment.
  • Patients with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix or other noninvasive or indolent malignancy that has previously undergone potentially curative therapy.
  • Patients with the following mood disorders as judged by the Investigator or a psychiatrist:
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
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  • ≥ CTCAE grade 3 anxiety
  • Impaired cardiac function or significant diseases, including but not limited to any of the following:
  • left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Congenital long QT syndrome
  • QTcF ≥ 480 msec on screening ECG
  • Unstable angina pectoris ≤ 3 months prior to starting study drug
  • Acute myocardial infarction ≤ 3 months prior to starting study drug
  • Patients with uncontrolled hypertension (defined as blood pressure of ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic at Screening)
  • Patients with:
  • unresolved diarrhea ≥ CTCAE grade 2, or
  • impairment of gastrointestinal (GI) function, or
  • GI disease that may significantly alter the absorption of TT-00420.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 5 half-lives or 3 weeks, whichever is shorter, (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug
  • Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy
  • Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants
  • Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers, or sensitive substrates of CYP3A4 ≤ 2 weeks prior to starting study drug.
  • Patients who are using a proton pump inhibitor within 4 days prior to the start of study therapy or a histamine-2 blocker within 2 days prior to the start of study therapy.
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled per investigator's discretion and Sponsor approval)
  • Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately controlled. For patients with known prior history of Hepatitis B or Hepatitis C, enrollment may be allowed per investigator's discretion and Sponsor approval.
  • Inability to swallow or tolerate oral medication
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.

Trial locations and contacts

32 sites in 1 country.

32 sites in 1 country

United States32 sites

  • Providence Cancer Center

    Anchorage, Alaska, 99508

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Maryland - Marlene and Stewart Greenebaum Cancer Center

    Baltimore, Maryland, 21250

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14203

  • Medical College of South Carolina

    Charleston, South Carolina, 29425

  • University of Chicago Medical Center - Duchossis Center for Advanced Medicine

    Chicago, Illinois, 60637-1426

  • University of Cincinnati Cancer Institute

    Cincinnati, Ohio, 45219

  • University Hospitals Seidman Cancer Center

    Cleveland, Ohio, 44106

  • Methodist Dallas Medical Center

    Dallas, Texas, 75203

  • Parkland Health & Hospital System

    Dallas, Texas, 75235

  • University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center

    Dallas, Texas, 75235

  • USO Oncology Network- Rocky Mountain Cancer Centers

    Denver, Colorado, 80218-1237

  • Henry Ford Health Center

    Detroit, Michigan, 48202

  • City of Hope

    Duarte, California, 91010

  • Summit Medical Group - Florham Park Campus

    Florham Park, New Jersey, 07932

  • Houston Methodist Hospital - Outpatient Center

    Houston, Texas, 77030

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • The University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • Comprehensive Cancer Center of Nevada

    Las Vegas, Nevada, 89169

  • University of Wisconsin School of Medicine and Public Health

    Madison, Wisconsin, 53705

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Sarah Cannon Research Institute at Tennessee Oncology

    Nashville, Tennessee, 37203

  • Ruttenberg Treatment Center - Mount Sinai

    New York, New York, 10029

  • USOR Oncology Network- New York Oncology

    New York, New York, 12208

  • USO Oncology Network-Virginia Oncology Associates - Brock Cancer Center - Norfolk

    Norfolk, Virginia, 23502-2824

  • USO Oncology Network-Northwest Cancer Specialists, P.C.

    Portland, Oregon, 97227

  • USO Oncology Network-Oncology and Hematology Associates of Southwest Virginia, Inc.

    Roanoke, Virginia, 24014

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California, Los Angeles, School of Medicine

    Santa Monica, California, 90404

  • Stony Brook University - Long Island Cancer Center

    Stony Brook, New York, 11794

  • USO Oncology Network-Texas Oncology

    Tyler, Texas, 75702-8363

Other trials in United States

About this study

Official title: A Phase II, Open Label, Multicenter Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) Tablet in Adult Patients With Advanced Cholangiocarcinoma

This study is an open-label, multicenter study to evaluate the efficacy and safety of TT-00420 tablet in adult patients with advanced cholangiocarcinoma.

Read the detailed description

This is a Phase II, open-label study to evaluate the efficacy and safety of TT00420 in patients with advanced/metastatic and surgically unresectable cholangiocarcinoma (CCA) with 1) FGFR 2 fusions who failed prior FGFR inhibitor treatment, 2) FGFR2 fusions who responded on prior FGFR inhibitor treatment, 3) with other FGFR alterations, or 4) whose tumors do not contain a detectable FGFR alteration.

Being tested
TT-00420
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TT-00420Drug

    TT-00420 tablet, administered orally once daily

Study groups in NCT04919642
Study groupRoleWhat they receive
Cohort A1ExperimentalFGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor
Receives: Drug: TT-00420
Cohort A2ExperimentalFGFR2 fusions who have previously responded on at least one previous treatment with an FGFR inhibitor and discontinued due to disease progression
Receives: Drug: TT-00420
Cohort BExperimentalOther FGFR alterations, including FGFR2 mutations and FGFR1/3 alterations, including fusions
Receives: Drug: TT-00420
Cohort CExperimentalNegative for FGFR alterations (FGFR wild-type)
Receives: Drug: TT-00420

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) in patients with FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor (Cohort A1)

    The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.

    Measured: Through study completion, an average of 9 months.

  2. ORR in patients with FGFR2 fusions who have responded (CR or PR) on at least one previous treatment with an FGFR inhibitor and discontinued due to progressive disease (Cohort A2)

    Measured: Through study completion, an average of 9 months.

  3. ORR in patients with FGFR alterations other than FGFR2 fusions (Cohort B)

    Measured: Through study completion, an average of 9 months.

  4. ORR in patients without FGFR alterations (wild-type FGFR mutation status) (Cohort C)

    Measured: Through study completion, an average of 9 months.

Secondary outcomes (6)

  1. ORR in all patients with FGFR alterations (Cohorts A and B)

    Measured: Through study completion, an average of 9 months.

  2. Progression Free Survival (PFS) (All Cohorts)

    Measured: From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

  3. Disease Control Rate (DCR) (All Cohorts)

    Defined as CR + PR + stable disease (SD)

    Measured: Through study completion, an average of 9 months.

  4. Overall Survival (OS) (All Cohorts)

    Measured: From first study drug administration until the date of death from any cause, assessed up to 24 months

  5. Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment (All Cohorts)

    As assessed per CTCAE version 5.0

    Measured: Up to 30 days from study discontinuation

  6. Concentration of TT-00420 at Protocol-Specified Timepoints (All Cohorts)

    Measured: From Cycle 1 to Cycle 4, an average of 4 months (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2021
  2. Study start7 Dec 2021
  3. Primary completion28 Feb 2024
  4. Study completion28 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04919642
Sponsor's protocol ID
TT420C1206
Status last verified
Dec 2023
First submitted
27 May 2021
Last updated
25 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Javle M, Fountzilas C, Liao CY, Pelster M, Li D, Deming D, Sahai V, Fonkoua LK, Cohn A, Mantry P, Richards D, Kingsley E, Wu F, Peng P, Hennessy K, Wang H, Sun C, Ni S, Fan J, Mahipal A. Tinengotinib for adults with advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2026 Feb;11(2):137-149. doi: 10.1016/S2468-1253(25)00230-4. Epub 2025 Dec 2.

    PubMed 41349554

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TT-00420 in people with Cholangiocarcinoma and FGFR2 Fusion, run by TransThera Sciences (Nanjing), Inc. at 32 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) in patients with FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor (Cohort A1) (time frame: Through study completion, an average of 9 months.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04919642, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.

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